Photocurable siloxane polymers

ABSTRACT

The present invention relates to photocurable siloxane polymers having functional acryl groups, useful in the preparation of intraocular lenses (IOLs). The polymers are siloxane copolymers, wherein the siloxane can be selected from the group consisting of diphenyl siloxane, phenylalkyl siloxane, dialkyl siloxane, and trifluoroalkyl alkyl siloxane. The invention also relates to methods for producing the said siloxane polymers, as well as to producing accommodating lenses in vivo, which means that the tens is formed in the capsular bag of the eye.

This application claims priority from provisional application Ser. No.60/105,580, filed Oct. 26, 1998.

FIELD OF INVENTION

The present invention relates to photocurable polysiloxanes polymers(silicones) having functional acryl groups, useful in the preparation ofintraocular lenses (IOLs). The invention also relates to methods forproducing elastomers comprising the said polymers, as well as to methodsfor producing accommodating lenses in vivo, which means that the lens isformed in the capsular bag of the eye.

BACKGROUND OF THE INVENTION

Implantation of an intraocular lens (IOL) following the extraction of acataract is now a standard ophthalmic procedure. The conventional IOLused to replace the natural lens is a fixed focus lens manufactured froma rigid plastic such as poly(methylmetliacrylate), PMMA, or from anelastomer, such as silicone. The implantation of such a lens usuallynecessitates the patient using spectacular correction for reading. Toovercome this limitation of the conventional IOL, increasing attentionhas been given to bifocal and multizonal lenses.

The technique of cataract explanation and lens replacement for anaccommodating IOL, an accommodating capsular lens. ACL, involves themetered injection of a low viscosity liquid, through a small incision(≈1 mm diameter), into the capsular bag, followed by its polymerizationunder forming pressure to create a lens of the required shape, using theform of the capsular bag as the mold. To reproduce the opticalperformance of the natural lens, the replacement lens will require arefractive index close to 1.41. To respond to the accommodating forcesof the eye, the compression modulus of IOL should be comparable to thatof the natural lens which is in the range of about 1 to 5 kPa. To designmaterials which balance the conflicting material's requirements of theACL requires the design of unique systems. These considerations have leda number of researchers to propose and to study the development of anACL. An accommodative re-fill lens is an IOL formed by filling thecapsular bag with the precursors of an elastomer, and causing, orallowing, the elastomer to set in the form of the natural lens.Thin-walled inflatable balloons, of silicone rubber, have also beendeveloped which can be inserted into the capsular bag and filled withthe desired system.

Most researchers of the development of the accommodative re-fill lenshave used silicone-derived systems for filling the capsular bag, eitherin the form of silicone oils or LTV (low temperature vulcanizing)silicone elastomers. Such systems suffer from disadvantages in thecontext of re-fill lens formation, the dimethyl silicones have arestricted refractive index (1.40), LTVs cure slowly, up to 12 hours maybe needed to complete their setting and their slow setting may result inmaterial loss from the capsular bag through the surgical incision,further, the high viscosities of some silicone oils and intermediatesmake their air-bubble free injection very difficult.

Injectable formulations of polysiloxanes for making an IOL directly inthe capsular bag of the human eye have been suggested in U.S. Pat. Nos.5,278,258, 5,391,590 ('590) and 5,411,553 to Gerace et al as well as inU.S. Pat. No. 5,116,369 (Kushibiki et al) These patents describemixtures of a vinyl-containing polyorganosiloxane, an organosiliconecomprising hydride groups and a platinum group metal catalyst which arecapable of being cured at ambient body temperature to an IOL inside thecapsular bag of the eye. These compositions suffer from the generaldrawback of low temperature curing in that the curing process isdifficult to control for the surgeon. The use of silicone fluids,demonstrating the principle of a silicone-based ACL, has been reportedby Haefliger, E. and Parel, J-M. (1994) J. Refractive and CornealSurgery 10, 550-555, but the gain in accommodation declined, probablybecause the system was not crosslinked.

Subsequently, the difficulties of introducing a thermally curingsilicone into the capsular bag have been demonstrated. A majordisadvantage of the use of a thermally curable system, such as one basedon Pt-cured vinyl addition, for the “mold-in-the-bag” approach isunderstood from a consideration of the three characteristic phases ofnetwork formation, viz. (a) pre-gelation; (b) gelation; and (c) curing.A lens can only be molded successfully in the pre-gelation phase, andonce the system has passed into its gelation phase it cannot be moldedwith precision. This is because the gel (polymer of infinite molecularweight) which is formed at and after the gel point has an elasticmemory, and so, regardless of the forming conditions, it will alwaysrevert to its original shape with time. When molding an IOL, or ACL,this recovery process becomes evident as surface defects, such asripples or wrinkles, which cause serious impairment of lens quality.When molding lenses from silicone systems, involving thermally inducedpolymerization, outside the body this phenomenon is easily regulated byadjusting the process variables of catalyst type and concentration,time, temperature and pressure. Molding an ACL within the eye duringsurgery imposes severe restrictions on the choice of these processvariables, the molding temperature is body temperature, the molding timeis the minimum compatible with the required residence time for any givenpatient upon the operating table, that is to say that ideally it must bevariable to meet the exigencies of the surgical demands of both theophthalmologist and the patient. In general terms, in a thermally curedsilicone system, such as those based on Pt-catalysts, the durations ofthe pre-gelation and cure phases are coupled, a system with a short curetime has a short pre-gelation time. It is generally regarded ascomplicated to lengthen the pre-gelation time without lengthening thecure time.

To comply with the difficulties of controlling the thermally inducedcuring it would be desirable to provide systems wherein the curing iscommand set by the surgeon. For this purpose photocurable (i.e.photopolymerization) compositions have been contemplated. EP 0414219describes an injectable system in which the liquid composition comprisesa difunctional acrylate and/or methacrylate ester and a photo initiatoractivated by light of 400-500 nm wavelength Hettlich et al (German J.Ophthalmol. vol. 1, 346-349, 1992) was amongst the first to propose theuse of photopolymerization of a monomer system as an alternativeapproach to setting the material within the capsular bag. He pointed tothe clinical success of blue light photocurable resins for dentalapplications and explored the use of such systems as injectablematerials for filling capsular bags from the eyes of cadaver pigs andlive rabbits. However, the systems used by Hettlich form materials withmoduli too high to allow accommodative processes. Further, theintroduction of acrylic monomers into the eye would be undesirable,since they are well-known to have high physiological activity.

Compositions comprising polysiloxanes with functional acrylic end groupswhich are curable with UV light have earlier been disclosed for themanufacture of contact lenses. Curable acrylic silicones per se haveindeed been known for a considerable time in various industrialapplications, as disclosed by U.S. Pat. Nos. 4,778,862 and 4,348,454.U.S. Pat. No. 5,321,108 and the Japanese patent specifications publishedas 3-257420, 4-159319 and 5-164995 disclose compositions ofacryl-terminated polysiloxanes suitable for contact lens production.However, the compositions for making contact lenses are unsuitable forintraocular lens production directly inside the human eye, whereinspecific considerations to the polysiloxanes must be taken in order toperfect an injectable lens forming material.

Consequently, there is a need for photocurable polymers and injectablecompositions thereof which are adapted to be included in a compositionsuitable for injection into the capsular bag of the human eye. Thepresent invention aims to perfect such polymers and compositionsincluding them, so they meet the necessary requirements for injectablelens materials.

DESCRIPTION OF THE INVENTION

It is an object of the present invention to provide photocurablepolysiloxane copolymers which can be polymerized to intraocular lensesin the presence of visible light, in particular blue light.

It is a particularly important object to provide such polysiloxaneswhich are adapted for injection directly into the capsular sac of thehuman eye directly in connection to that the defect natural crystallinelens has been surgically removed.

It is another important object of the invention to provide compositionsof said polysiloxanes together with a photoinitiator and furthercomplementary additives necessary for forming the solid elastomer lensby final curing in the capsular sac.

In a general aspect the present invention relates to an polysiloxanecopolymer having functional acryl groups which are capable of beingphotopolymerized into a solid intraocular lens with a specific gravitygreater than about 1.0 and with a refractive index suitable forrestoring the refractive power of the natural crystalline lens. For thispurpose, the polysiloxane copolymer has siloxane monomer units areselected among substituted or unsubstituted arylsiloxanes,arylalkylsiloxanes, alkyl(alkyl)siloxanes of the general formula—R_(a)R_(b)SiO—. In order to accomplish suitably high refractive indicesof the polysiloxane copolymer, it is preferable that one siloxanemonomer unit is an arylsiloxane or an arylakylsiloxane, more preferablydiphenyl siloxane or phenylmethylsiloxane. It is also highly preferredthat said substitutions are fluorosubstitutions, in particular it ispreferred that one siloxane monomer unit incorporates a fluroroalkylgroup, more preferably one siloxane monomer isfluoroalkyl(alkyl)siloxane. According to a preferred aspect, the amountof fluoroalkyl(alkyl)siloxane units exceeds about 4 mol %. This enablesa special advantage of the inventive polysiloxanes by providing themwith higher specific gravity than conventional polysiloxanes reported inophthalmic use.

Functional acryl groups are defined herein by that at the polysiloxanemolecules have functional groups attached thereto including an acrylgroup moiety, so as to become acryl-bearing, by acryl attachment to thesiloxane monomers of the polysiloxane backbone, its terminal ends, orboth. The acryl groups in said functional groups can be linked to thesilicone atoms by spacers. Examples of functional acryl groups includeacrylamidopropyl, methacrylamidopropyl, acryloxyhexyl andmethacryloxyhexyl. Preferably, the functional acryl groups are attachedto the terminal ends of polysiloxane molecules, as exemplified byacrylamidopropyl-, methacrylamidopropyl-, acryloxyhexyl- andmethacryloxyhexyl-terminated polysiloxanes. Those skilled in the art canconsider numerous such alternatives which maintain the basic function ofhaving an acryl group for subsequent crosslinking/polymerization of thepolysiloxane molecules into larger network together with aphotoinitiator. In the same manner it is also to be understood that themeaning of acryl group should include acryl or substituted acryl, suchas methacryl, moieties attached through a variety of linkages includingester, amide and urethane linkages, or functional analogues of acrylcapable of undergoing crosslinking reactions with a photoinitiator.

In a further aspect, the invention relates to a process for productionof polysiloxane copolymer having functional acryl groups, as describedabove. Such a process is generally described in the Examples below andthe skilled person will be able to make suitable modifications in orderto prepare other copolymers within the scope of the invention.

The polysiloxane copolymers having functional acryl groups according tothe present invention should preferably have a refractive index aboveabout 1.39 in order to restore the refractive index of the natural lenswhich has a refractive index of about 1.41. It is an important aspect ofthe present invention to be able to control the refractive index ofpolysiloxanes by selection of its siloxane monomer composition andthereby the refractive outcome of the final implanted lens. It is to beunderstood that refractive indices can be up to about 1.60 is within thecontext of the present application if this is required for a specificoptical application. This further considered in the co-pendingInternational Patent Application with even filing date claiming priorityfrom U.S. patent application Ser. No. 09/170,160 which hereby isincorporated as a reference.

According to a preferred aspect of the present invention, thepolysiloxane copolymer having functional acryl groups can be obtainedfrom a copolymer having the general formula:

wherein R¹ and R² are independently C₁-C₆ alkyl; R³ is phenyl; R⁴ isphenyl or C₁-C₆ alkyl; R⁵ is CF₃(CH₂)_(x) wherein x is 1-5; R⁶ is C₁-C₆alkyl or fluoroalkyl; 1 is in the molar fraction range of 0 to 0.95; mis in the molar fraction range of 0 to 0.7; and n is in the molarfraction range of 0 to 0.65, the copolymer having functional acrylgroups at the terminal ends thereof. In one embodiment, m is in themolar fraction range of from greater than 0 to 0.7; and n is in themolar fraction range of from greater than 0 to 0.65.

It is preferred that R¹ is methyl, that R² is methyl, R⁴ is phenyl, thatx is 2, either independently, or in combination.

Preferably according to these alternatives R⁶ is methyl. According toone embodiment, the polysiloxane is a copolymer of diphenyl orphenylalkyl siloxane and dialkyl siloxane with terminal acryl groups.According to further embodiments, the polysiloxane is a copolymer ofdiphenyl or phenylalkyl siloxane and trifluoroalkyl(alkyl)siloxane, or aterpolymer or higher order polymer of diphenyl and/or phenylalkylsiloxane, dialkyl siloxane and trifluoroalkyl alkyl siloxane. Accordingto a specific preferred embodiment, polysiloxane is an acryl-terminatedterpolymer of dimethyl siloxane, diphenyl siloxane or phenylmethylsiloxane and 3,3,3-trifluoropropylmethyl siloxane. Preferably, saidpolysiloxanes comprise at least about 4 mol % of trifluoropropylmethylsiloxane and 1 to 50 mol % of diphenylsiloxane and/orphenylmethylsiloxane. More preferably said polysiloxanes comprise about4 to 65 mol % trifluoropropylmethyl siloxane, 1 to 50 mol % ofdiphenylsiloxaue and dimethylsiloxane monomer units. One suitableacryl-terminated polysiloxane composition comprises about 28 mol %trifluoropropylmethyl siloxane, about 4 mol % diphenyl siloxane anddimethyl siloxane monomer units.

The invention also relates to an injectable lens material having asuitable viscosity to be injected through standard cannula with an 18Gauge needle or finer. For this purpose the material should preferablyhave a viscosity lower than about 60 000 cSt or below about 8000 cSt forbeing readily injectable through a 21 Gauge needle. The injectable lensmaterial is composition of at least one type of polysiloxanes accordingto any of the definitions above, a photoinitiator, optionally acrosslinking agent, which in itself can be siloxane oligoimer or polymerhaving functional acryl groups and further physiologically orophthalmologically acceptable additives necessary for producing a lens.The composition is preferably formed as fluid mixture from separatelystored constituents which are protected from reactivity during storage.This type of kits or multi-chamber cartridges with mixing equipment andtheir operation are well known in the art of pharmaceuticals or siliconeproducts and will not be discussed here in further detail. To reducephysiological hazards, only acryl-substituted siloxane polymers areintroduced into the capsular bag, together with medically acceptablephotoinitiators activated in the visible range, including blue lightactivated types derived from acyl phosphine oxides and bisacylphosphineoxides, in low molecular weight and high molecular weight (polymeric)forms, and titianocene-photoinitiators. Important characteristics ofthese photoinitiators for injectable lens applications are that theyinitiate the photopolymerization of acryl groups when exposed to visiblelight, preferably blue light and that they are “photobleaching” and sothey are efficient as photoinitiators for the rapid curing of thicksections (1-5 mm). Suitable photoinitiators for injectable lens formingcompositions are also discussed in WO 99/47185 and in the Swedish PatentApplication No. 9900935-9 which both are incorporated herein asreferences. For the embodiment discussed in said Swedish PatentApplication No. 9900935-9, wherein the photoinitiator is a conjugate ofa photoactive groups and a macromolecule capable of participating in acrosslinking reaction with acryl-terminated polysiloxanes, themacromolecule in such a photocrosslinker should be a polysiloxanecompatible with said first polysiloxanes. The injectable lens materialcomposition can also comprise said polysiloxanes having functional acrylgroups, a photoinitiator according to above and a separate crosslinkingagent. Suitable crosslinking agents can be found among di- or tri- andhigher order acrylates, methacrylates, acrylamides, methacrylamidesincluding siloxane oligomers and polymers having functional acrylgroups. Short molecule crosslinkers are exemplified by hexanediolacrylate, tripropyleneglycol diacrylate. Polymeric crosslinkers,suitable for injectable IOL applications are exemplified by copolymersor higher order polymers incorporating(methacryloxypropyl)methylsiloxane units.

Further, the invention relates to a method of producing an elastomer,preferably an intraocular lens, by preparing polysiloxane copolymerswith functional acryl groups as previously defined, mixing saidcopolymers with a photoinitiator and optionally a crosslinking agent,injecting said mixture into a lens forming mold, irradiating theinjected mixture with light so as to form the solid elastomer. Mostpreferably, according to the present invention the mixture is injectedinto the human eye to form an implant to replace the natural lens, butthe method is also conceivable in non-surgical processes, such asconventional lens manufacturing with injection molding.

A method of in vivo production of an intraocular lens, will comprise thesteps of preparing an polysiloxane copolymer having functional acrylgroups according to the invention; mixing said copolymer and aphotoinitiator, preferably a medically acceptable blue lightphotoinitiator, to a composition; injecting said composition comprisingsaid copolymer and photoinitiator into the capsular bag of the eye; andinitiating a polymerization reaction to create a lens in the capsularbag.

The invention also relates to an elastomer manufactured by the processdescribed above. Preferably, such an elastomer is in the form of anoptical lens, which preferably has a refractive index between 1.39 and1.46, or, more preferably, close to 1.41. To obtain optical lenseshaving the desired refractive index, the proportions between thecopolymer precursors should preferably be close to the proportionsdemonstrated in the Examples given below. However, as mentioned above itis possible to obtain higher lenses with higher refractive indices up toabout 1.60 according to the present invention if this is necessary toobtain specific refraction values in certain clinical applications.Further, by employing the polysiloxanes with functional acryl groups,the injectable material and the methods of the present invention lenseswith a compression modulus suitable to undergo accommodation by theforces of the eye can be obtained. Typically, lenses having a modulusbelow about 55 kPa and in the range of about 20 to 50 kPa can readily beobtained by employing the present invention which are functionallyaccommodatable by the human eye. Optionally, the elastomer according tothe invention can also comprise an UV absorbing compound or otherconventional additives known to those skilled in the art.

The invention further relates to a medicinal kit consisting of part (a)comprising polysiloxane copolymers having functional acryl groupsaccording to the invention; and a part (b) comprising a clinicallyacceptable photoinitiator. The combination gives liquid siliconepolymers of controlled photo-reactivity that can be “command set” byphotopolymerization, upon exposure to blue light. The specification ofthis photo-crosslinkable system derives from an interplay of theviscosity and the injection density of the initial polymer solution, aswell as the refractive index, modulus and compressive characteristics ofthe photocured gel.

A special advantage of the materials of this invention is that theincorporation of a fluoroalkyl siloxane enables materials of higherspecific gravity to be produced than has previously been reported insilicones for ophthalmic use. Polydimethylsiloxane (PDMS), havingrefractive index 1.403 and specific gravity ca. 0.97-0.98, has beenreported as a material for an injectable IOL. However, whilst therefractive index of PDMS approximately matches that of the human lens,the lower specific gravity of PDMS can present considerable difficultyfor the surgeon as PDMS floats in aqueous solution. This makes completefilling of the capsular bag with exclusion of aqueous fluid difficult inthe case of direct injection. Copolymers of dimethyl and diphenylsiloxanes have higher specific gravity than PDMS. However, the diphenylcontent of the copolymers increases the refractive index, thus, forexample, it is not possible to have a dimethyl-diphenyl copolymer with aspecific gravity greater than 1.0 and a refractive index of less thanapproximately 1.44. Materials of the present invention, beingcopolymers, terpolymers or higher order polymers, incorporatingfluoroalkyl siloxane units, enable silicones of specific gravity greaterthan 1.0 to be produced over a wider range of refractive index than haspreviously been reported.

DETAILED AND EXEMPLIFYING PART OF THE DESCRIPTION

The following examples aim to illustrate methods of preparingpolysiloxanes having functional acryl groups and their subsequentphotopolymerization. The preparation of acryl terminated siloxanes ingeneral has been well reported (see Thomas, D. R.: p.610 in “SiloxanePolymers” (Clarson, S. J. and Semlyen. J. A., eds.) New Jersey, 1993)and the examples given below are those preferred of the many routes. Thepreparation of acrylic terminated terpolymers ofdimethylsiloxane/diphenyl-siloxane/methyl,3,3,3-trifluoropropylsiloxanehave not been reported.

EXAMPLE 1 Preparation of aminopropyl-terminatedpoly(dimethyl-co-diphenyl)siloxane

Distilled octamethylcyclotetrasiloxane (27.5 g, 92.9 mmol, 82.1 mol %),recrystallised octaphenylcyclotetrasiloxane (16.1 g, 20.3 mmol, 17.9 mol%), and 1,3-bis(3-aminopropyl)tetramethyldisiloxane (0.641 g, 2.73 mmol)were carefully charged to a three-necked flask. The flask was equippedwith a mechanical stirrer, purged with nitrogen then potassium hydroxide(80 mg) catalyst was added. The reaction mixture was heated to 160° C.and stirred 24 h. The catalyst was then neutralized by the addition of0.24 g of 36% HCl aq. as a solution in 3 ml ethanol, with stirring, andthe mixture cooled to 25° C. The clear colourless silicone fluidobtained was diluted with 100 ml diethyl ether and transferred to aseparating funnel. After extracting twice with 100 ml portions water toremove the catalyst, the solution was dried with magnesium sulphate. Theproduct was filtered, and the solvent evaporated. The clear viscousfluid was heated to 110° C. in vacuo (0.2 torr) to remove residualsolvent and volatile products. Yield was 42.05 g (95%).

EXAMPLE 2 Preparation of aminopropyl-terminatedpoly(dimethyl-co-diphenyl-co-trifluoropropylmethyl)siloxane

Distilled octamethylcyclotetrasiloxane (83.56 g, 0.282 mol),octaphenylcyclotetrasiloxane (11.77 g, 0.0148 mol), and distilled3,3,3-trifluoropropylmethylcyclotrisiloxane (27.56 g, 0.0588 mol) wereweighed to a flask and dried under vacuum, at 80° C. for 30 minutes. Theflask was purged with nitrogen and1,3bis(3-aminopropyl)tetramethyldisiloxane (3.107 g, 0.0125 mol)end-capper was injected via a septum. Potassium silanolate initiator(0.055 g) was added, the temperature raised to 160° C., and mixtureheated and stirred for 36 hours. The clear colourless product wasallowed to cool, diluted with 57 ml chloroform and washed: three timeswith 88 ml portions water; twice with 88 ml portions methanol; then theproduct was diluted with 44 ml tetrahydrofuran and washed twice morewith 88 ml portions methanol. Solvent and volatiles were stripped byheating at 100° C. under vacuum (pressure falling to <1 mbar). Theproduct obtained was clear and colourless. Yield: 90.72 g (71.9%).Analysis showed refractive index at 25° C.: 1.417 (theory. 1.417),density: 1.048 g/ml (theory: 1.059), and molecular weights by gelpermeation chromatography (GPC) with polystyrene standards: Mn 25,900 Mw71,800. (The high polydispersity shown in the GPC results suggestreaction was still not fully complete after 36-40 hours; this problemcould be improved by use of a bisaminosiloxane oligomeric end-capper).Polymer unit ratios by H-NMR, 500 MHz, dimethyl/diphenyl/trifluoropropylwere: 0.816/0.047/0.137 (starting monomer ratios were:0.792/0.042/0.165). Amino-terminated polysiloxanes, prepared by thisroute were used as starting material for preparing acrylamidoalkyl- andmethacrylamidoalkyl-terminated silicones.

EXAMPLE 3 Preparation of aminopropyl-terminatedpoly(dimethyl-co-diphenyl-co-trifluoropropylmethyl)siloxane

Example 2 was repeated with different monomer combinations:octamethylcyclotetrasiloxane (84.54 g, 0.285 mol),octaphenylcyclotetrasiloxane (16.15 g, 0.0204 mol), and distilled3,3,3-trifluoropropylmethylcyclotrisiloxane (21.20 g, 0.0452 mol),1,3-bis(3-aminopropyl)tetramethyldisiloxane (3.118 g, 0.0125 molpotassium silanolate initiator (0.056 g). Yield was 88.44 g (70.6%).Analysis showed refractive index at 25° C.: 1.425 (theory: 1.426),density: 1.046 g/ml (theory: 1.051), and molecular weights: Mn 19,600 Mw69,400. Polymer unit ratios by H-NMR dimethyl/diphenyl/trifluoropropylwere: 0.832/0.065/0.104 (starting monomer ratios were:0.813/0.058/0.129).

EXAMPLE 4 Preparation of aminopropyl-terminatedpoly(dimethyl-co-diphenyl-co-trifluoropropylmethyl)siloxane

Example 2 was repeated with different monomer combinations:octamethylcyclotetrasiloxane (62.66 g, 0.211 mol),octaphenylcyclotetrasiloxane (34.38 g, 0.0433 mol) and distilled3,3,3-trifluoropropylmethylcyclotrisiloxane (24.87 g, 0.0531 mol),1,3-bis(3-aminopropyl)tetramethyldisiloxane (3.327 g, 0.0134 mol)potassium silanolate initiator (0.055 g). Yield was 77.07 g (61.0%).Analysis showed refractive index at 25° C.: 1.455 (theory: 1.456),density: 1.083 g/ml (theory: 1.090). Polymer unit ratios by NMR,dimethyl/diphenyl/trifluoropropyl were: 0.696/0.161/0.143 (startingmonomer ratios were: 0.686/0.141/0.173).

EXAMPLE 5 Preparation of hydroxyhexyl-terminatedpoly(dimethyl-co-diphenyl)siloxane

Distilled octamethylcyclotetrasiloxane (27.54 g, 92.9 mmol, 82.1 mol %)and recrystallised octaphenylcyclotetrasiloxane (16.11 g, 20.3 mmol,17.9 mol %) were carefully charged into a three-necked flask. Thereactor was equipped with a mechanical stirrer; purged with nitrogen,and tetramethylammonium hydroxide (60 mg) catalyst added. The reactionmixture was heated to 110° C. with stirring for 2 hours, becomingviscous, followed by 3 hours heating at 160° C. to decompose thetetramethylammonium hydroxide catalyst.1,3-Bis(6-hydroxyhexyl)tetramethyldisiloxane (0.916 g, 2.74 mmol)end-capper (calculated Mn: 16,000) and 1 ml trifluoromethanesulfonicacid catalyst were added and the mixture stirred 6 hours at 60° C. Theresulting viscous fluid was diluted with 100 ml tetrahydrofuran andvigorously stirred with 5% sodium hydroxide at 25° C. in order todeliberate the hydroxyl end group. The saponification process wasmonitored by IR spectroscopy, samples being withdrawn from time to time.After 12 hours the process was 95% complete by IR. (Longer time riskedcleavage of the end group by a base catalysed process). The mixture wastransferred to a separating funnel, the two phases separated, and theorganic layer washed with water (3×100 ml). The solution was dried withfirst sodium sulphate then magnesiun sulphate, and filtered. Afterinitial evaporation of the solvent, the clear viscous fluid was heatedto 110° C. in vacuo (0.2 torr) to remove residual solvent and somevolatile products, affording a colourless viscous fluid end product.Yield: 32.81 g (73.6%). The copolymer unit composition by 1H-NMR (400MHz, CDCl₃) was 17.9 mol % diphenyl-units before vacuum treatment, and19.1 mol % after. Hydroxy-terminated polysiloxane, prepared by thisroute can be used as starting material for preparing acryloxy- andmethacryloxy-terminated silicones.

EXAMPLE 6 Preparation of acrylamidopropyl-terminatedpoly(dimethyl-co-diphenyl)siloxane

Aminopropyl-terminated poly(dimethyl-co-diphenyl)siloxane (40 g, 4.25meq) as prepared in Example 1, was dissolved in 100 ml drydichloromethane and 2 g calcium hydride was added in three portions. Themixture was cooled to 0° C. and acryloyl chloride (640 mg, 570 μl, 7.0mmol) was added. The suspension was stirred over night, and the calciumhydride and calcium chloride were removed by filtration. The filtratewas washed with water (100 ml) then dried with sodium sulphate (latermagnesium sulphate). Solvent was evaporated, first at 20 torr then at0.2 torr, at room temperature. This sample was used for rheologymeasurements and injection into a pig cadaver eye. However, subsequentGPC analysis showed cyclic impurities to be present, so further washingwas performed. A portion of sample, 20.35 g, was diluted with 20 mltoluene and the solution precipitated to stirred methanol. The siliconewas allowed to separate, and again diluted with toluene and precipitatedto methanol, as before. The silicone was transferred to a flask, and thesolvent removed under vacuum (to 1.5 mbar) with gentle heating instages. This sample is referred to as Example 6 ‘post-washing’.Acrylamidopropyl end groups by NMR (500 MHz) gave Mn 21,000 (0.095meq/g).

EXAMPLE 7 Preparation of acrylamidopropyl-terminatedpoly(dimethyl-co-diphenyl-co-trifluoropropylmethyl)siloxane

Aminopropyl-terminated terpolymer of Example 2 (15.02 g, 1.50 mmol basedon theoretic Mn 10,000) was weighed to a dried flask, and nitrogen flowapplied. Dried dichloromethane (40 ml) was added, followed by calciumhydride (1 g), added in small portions. The flask was cooled inice-water until the temperature of the contents was 0° C., thendistilled acryloyl chloride (0.380 g, 4.2 mmol) was added via a septum.The reaction was stirred for 30 minutes at 0° C. then the ice wasremoved and the mixture allowed to warm to ambient over 3.5 hours. Theturbid mixture was filtered under reduced pressure, with dichloromethanerinsing, to remove CaH₇ and CaCl₂. The solution was washed with 50 mlwater, dried over magnesium sulphate, and the solvent removed undervacuum, initially on a rotary evaporator then on a bath at 50° C. withpressure to <1 mbar. Yield: 13.28 g (87%). The H-NMR spectrum showedunattached acrylic reagent to be present, so the product wasre-precipitated twice, each time with dilution in 20 ml dichloromethaneand precipitation to 200 ml stirred methanol. Solvent was then removedunder vacuum as before, giving a clear colourless product. Yield: 6.43 g(42%). Analysis by 500 MHz H-NMR showed no unattached acrylic reagentand gave unit ratiosdimethylsiloxane-/diphenyl-/trifluoropropyl-/acrylamide of0.817/0.0468/0.131/0.0102 implying Mn 17,800. Conversion of the aminogroups appeared quantitative.

EXAMPLE 8 Preparation of methacrylamidopropyl-terminatedpoly(dimethyl-co-diphenyl-co-trifluoropropylmethyl)siloxane

Example 6 was repeated using methacryloyl chloride as modificationreagent. Aminopropyl-terminated terpolymer of Example 3 (15.11 g, 1.50mmol based on theoretic Mn 10,000) was reacted with distilledmethacryloyl chloride (0.439 g, 4.2 mmol), other reagents and the methodbeing the identical. The final yield was 10.06 g (66%). Analysis by 500MHz H-NMR gave unit ratiosdimethylsiloxane/diphenyl-/trifluoropropyl-/acrylamide of0.827/0.064/0.099/0.0105 implying Mn 17,200. Again conversion of theamino groups appeared quantitative.

EXAMPLE 9 Rheological Measurements of Photocured Materials

Silicones prepared as above (Examples 6, 7, & 8) were photocured by bluelight and colourless glass-clear elastomers were produced, and theirmoduli measured. Comparison has been made with elastomers fromcommercially available photocurable silicones, and measurements madeboth with and without an additional crosslinker. Compositions forrheological testing were prepared in ca.3 g batches under subdued light,with weighing to ±0.01 mg. To ensure dissolution in the silicone, thephotoinitiator was first dissolved in 1-1.5 ml dichloromethane and thissolution was stirred for 3 minutes with the silicone, then the solventremoved by vacuum desiccation to constant weight at room temperature(typically ca.30 minutes with pressure to 0.3 mbar). Disks for analysiswere cast in a Teflon mould (diameter 25 mm, depth 1.0 mm) which wasfilled with the composition and then covered with a microscope slide, soas to give a smooth contact surface over the entire diameter of themould, and the composition was then cured using blue light. (Source wasa Vivadent Heliolux DLX dental gun, emitting 400-525 nm, placed 22 mmabove the mould, at which distance the light intensity was 13-14mW/cm²). Measurements of the shear (storage) modulus were then performedon the disks using a Rheometrics RDA 2 rheometer at 35° C. Aphotoinitiator active in the blue light region was used:bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide (Ciba Irgacure 819).The photoinitiator concentration used was 0.20 % ww in all the examplesquoted herein. For comparison, studies were also made of commercialphotocuring silicones: methacryloxypropyl-terminatedpolydimethylsiloxane (Gelest-ABCR DMS-R31), Mn 24,800 by NMR, 0.081meq/g methacryloxy; and acryloxy-terminated polydimethylsiloxane(Gelest-ABCR DMS-U22), Mn 768 by NMR, 2.60 meq/g acryloxy, which becauseof its low Mn was here employed as a crosslinker. An alkyl crosslinker,tripropyleneglycol diacrylate, TPGDA (Genomer 1230), was also used.

Crosslinker Examp % w Shear modulus le Silicone polymer type w G′/kPa at35° C. 9(a) Methacryloxypropyl-terminated — — 21.0 polydimethylsiloxaneABCR DMS-R31 9(b) ″ TPGDA 0.57 46.1 9(c) ″ ″ 1.14 48.1 9(d) ″ Acryloxy-0.76 45.3 terminated polydimethylsiloxa ne ABCR DMS- U22 9(e)Acrylamidopropyl-terminated — — 46.5 poly(dimethyl-co- diphenyl)siloxane(Example 6) 9(f) ″ TPGDA 1.05 51.6 9(g) ″ (Example 6: post washing) — —52.7 9(h) Acrylamidopropyl-terminated — — 55.8poly(dimethyl-co-diphenyl-co- trifluoropropyl)siloxane (Eample7) 9(i) ″(Example 8) — — 65.3

EXAMPLE 10 Preparation of a Photocured Intracular Lens

Acrylamidopropyl-terminated poly(dimethyl-co-diphenyl)siloxane (Example2) containing photoinitiator (Irgacure 819, 0.20% ww) and crosslinker(TPGDA, 0.57%) was prepared as per Example 9(b). A fresh pig cadaver eyewas prepared, with small aperture incision into the capsular bag andremoval of the crystalline lens. The silicone composition was injectedinto the capsular bag via a 21 gauge cannula, so as to refill the bagand give appropriate curvature. The silicone was cured by blue lightfrom a Vivadent Heliolux DLX dental gun placed 0.5-1.0 cm in front ofthe cornea, and the lens was extracted to enable examination. The clearcolourless tack-free lens had anterior radius 12.0±0.5 mm, posteriorradius 5.19±0.1 mm thickness 5.06±0.02 mm, diameter 8.9±0.1 mm. Itspower in air was 108±2 diopter, and focal length 9.2±0.2 mm (in water:27.1±0.5 diopter, and focal length 37.0±0.7mm).

EXAMPLE 11 Example 11.1 (a) Preparation ofdimethylsiloxane/diphenylsiloxane/methyl,3,3,3 -trifluoropropylsiloxaneterpolymers

Octamethylcyclotetrasiloxane (D4) (6.0 g, 20 mmoles),octaphenyl-cyclotetrasiloxane (DPh4) (1.7 g, 2 mmoles) andtrimethyl-tris(3,3,3-trifluoropropyl)cyclotrisiloxane (23% cis and 77%trans, F3) (7.3 g, 16 mmoles) were added tobis(3-aminopropyl)dimethyldisiloxane (0.15 to 0.3 g), and purged withargon. The temperature was raised to +120° C. andbis(tetramethylammonium)-polydimethylsiloxanolate catalyst (0.01 g)added, and the reaction heated for 2-3 h at +120° C. and 3 h at +160° C.Upon cooling to ambient temperature the polymer was dissolved intetrahydrofuran and precipitated and washed with methanol, centrifuged,and dried in vacua. The resulting polysiloxane had a number averagemolecular weight>10 kDa, a refractive index>1.40 and a density>1.10.

(b) Introduction of Acrylic Groups

A dimethylsiloxane/diphenylsiloxane/methyl,3,3,3-trifluoropropylsiloxaneterpolymer, from type (a) preparations above, (4.0 g, 0.04 mmoles) wasdissolved in methylene dichloride to yield a 10-20 weight % solution, anexcess of finely divided CaH added and the resulting suspension cooledto 0° C. and purged with argon. Acryloyl chloride (0.15 g, 0.14 mmoles)dissolve in methylene dichloride (3 ml) was added dropwise, withstirring and cooling to ensure that the temperature of reaction did notrise above 0° C. After complete addition of the acryloyl chloride thesolution was stirred for 4 h and allowed to warm to ambient temperature.The suspension was filtered and the filtrate neutralized with NaHCO₃,washed with water, dried over anhydrous MgSO₄, and evaporated in vacuo.The resulting acrylic-terminated terpolymer was stabilized by theaddition of 1-3 ppm of hydroquinone. The resulting polysiloxane can bephotopolymerized to form flexible lenses of very low modulus, byexposure to blue light whilst retained in a suitable mold, such as acadaver pig's eye capsular bag, or a silicone balloon, or a transparentplastic mold. The photoinitiation is caused by the inclusion of e.g. 2%TMPO prior to isolation of the siloxane which was completed in theabsence of blue light.

Example 11.2 (a) Formation of Polysiloxane, Silanol-terminated

Hexamethylcyclotrisiloxane (D3) (6.0 g, 27 mmoles),hexaphenyl-cyclotrisiloxane (DPh3) (1.7 g, 2.7 mmoles) andtrimethyl-tris(3,3,3-trifluoropropyl)cyclotrisiloxane (cis and trans F3)(7.3 g, 21 mmoles) were dissolved in methylene chloride to which wasadded trimethylsilyl triflate (TMST) (0.23 g) and 2,6-di-t-butylpyridine(0.15 to 0.2 g), and purged with dry argon. Terpolymerization proceededat ambient temperature and was completed within 24 h. The polymerizationproceeds by a non-terminating chain growth mechanism and so themolecular weight of the copolymers was dependent upon the ratio monomersto TMST, the reaction was terminated by the addition of an excess (overTMST) of NaHCO₃. The resulting terpolymer solution was washed withdilute HCl (0.2 M) and with water (3X), dried over anhydrous MgSO₄, andsolvent and residual cyclics removed by vacuum distillation at lowtemperature. The siloxane terpolymer had a number average molecularweight>10 kDa, a refractive index>1.40 and a density>1.10. Instead ofTMST, trifluoromethanesulphonic acid (triflic acid) and its derivatives,e.g. benzyldimethyl triflate, can be used.

(b) Preparation of Acrylic Terminated Terpolymer Silanols

The silanol terminated terpolymer of hexamethyl-cyclotrisiloxane (D3),hexaphenylcyclotrisiloxane (DPh3) andtrimethyltris(3,3,3-trifluoropropyl)cyclotrisiloxane (cis and trans F3)was mixed with acryloxymethyldimethyl-acryloxysilane (prepared asdescribed by Chu et al. in U.S. Pat. No. 5,179,134, 1993, to LoctiteCorporation) in equimolar ratio, at ambient temperature. After standingfor 2 h the by-product, acrylic acid was removed by vacuum stripping.

Example 11.3

A silanol terminated dimethyldiphenylsiloxane (viscosity 2000-3000 cSt;molecular weight 35 kDa mole % diphenyl-siloxane 1-2) (4.0 g, 0.12mmoles) was dissolved in methylene chloride to yield a 15 weightsolution, and an excess of finely divided CaH was added. The resultingsolution was purged with argon and cooled to 0° C., whenacetoxy(bisacryloethyl)methylsilane (0.15 g, 1.4 mmoles) dissolved inmethylene chloride, together with an addition of 50 ppm of dibutyltindilaurate, was added dropwise with stirring. Stirring the reaction wascontinued for a further 4 h and the resulting suspension was filtered.The filtrate was dried over anhydrous Mg₂SO₄ and evaporated to drynessin vacuo.

EXAMPLE 12 Photopolymerization of Acryl-terminated PolysiloxaneTerpolymers

A number of visible light photoinitiators is available for initiatingthe acrylic photopolymerization of the acrylic-terminated D3/DPh3/F3terpolymers described above, and these include titanocenes, such asbis(h⁵-cyclopentadienyl)-bis[2,6-difluoro-3-(1H-pyr-1-yl)phenyl]titanium(Til), and acylphosphine oxides, such as2,4,6-trimethylbenzoyl-diphenylphosphine oxide (TMPO), and polymervariants such as Lucirin (a polymeric derivative of TMPO; see Angiolini,L. et al. (1995) J. Appl. Polym. Sci. 57, 519).

Example 12.1

Acrylic-terminated D3/DPh3/F3 terpolymer and Til (0.5%) were mixed andirradiated with light from a 488 nm A-laser. The combination gelledrapidly to yield an elastomer of low modulus, a refractive index>1.40and a density>1.10.

Example 12.2

Acrylic-terminated D3/DPh3/F3 terpolymer and TMPO (3.0%) were mixed andirradiated with light from a blue light gun. The combination gelledrapidly (less than 3 min) to yield an elastomer of low modulus, arefractive index>1.40 and a density>1.10.

Example 12.3

Acrylic-terminated D3/DPh3/F3 terpolymer and Lucirin (2%) were mixed andirradiated with a blue light gun. The combination gelled rapidly toyield an elastomer of low modulus, a refractive index>1.40 and adensity>1.10.

What is claimed is:
 1. An injectable lens material having suitableviscosity for being injected through standard cannula and comprising amixture of a polysiloxane copolymer, a photoinitiator, and, optionally,a crosslinking agent, wherein the polysiloxane copolymer is capable ofbeing photopolymerized into a solid intraocular lens and has functionalacryl groups at terminal ends of the copolymer, a specific gravitygreater than about 1.0, a refractive index suitable for restoring therefractive power of the natural crystalline lens, and siloxane monomerunits in the polysiloxane copolymer selected from the group consistingof substituted and unsubstituted arylsiloxanes, substituted andunsubstituted arylalkylsiloxanes, and substituted and unsubstitutedalkyl(alkyl)siloxanes, and mixtures thereof, wherein at least one of thesiloxane monomer units is substituted with one or more fluorine atoms,and wherein at least one siloxane monomer unit is an arylsiloxane or anarylalkylsiloxane.
 2. An injectable lens material according to claim 1,wherein the copolymer has a refractive index above about 1.39.
 3. Aninjectable lens material according to claim 1, wherein the copolymer hasa backbone of the general formula:

wherein R¹ and R² are independently C₁-C₆ alkyl; R³ is phenyl; R⁴ isphenyl or C₁-C₆ alkyl; R⁵ is CF₃(CH₂)_(x) wherein x is 1-5; R⁶ is C₁-C₆alkyl or fluoroalkyl; l is in the molar fraction range of 0 to 0.95; mis in the molar fraction range of from greater than 0 to 0.7; and n isin the molar fraction range of from greater than 0 to 0.65.
 4. Aninjectable lens material according to claim 3, wherein R¹ is methyl. 5.An injectable lens material according to claim 4, wherein R² is methyl.6. An injectable lens material according to claim 3, wherein R⁴ isphenyl.
 7. An injectable lens material according to claim 3, wherein xis
 2. 8. An injectable lens material according to claim 3, wherein R⁶ ismethyl.
 9. An injectable lens material according to claim 3, wherein lis in the molar fraction of greater than
 0. 10. An injectable lensmaterial according to claim 3, wherein the copolymer is a copolymer ofdiphenyl siloxane or phenylalkyl siloxane units and trifluoroalkyl alkylsiloxane units.
 11. An injectable lens material according to claim 3,wherein the copolymer is a terpolymer or higher order copolymer ofdiphenyl or phenylalkyl siloxane, dialkyl siloxane and trifluoroalkylalkyl siloxane.
 12. An injectable lens material according to claim 3,wherein the copolymer is a terpolymer of dimethyl siloxane, diphenylsiloxane and trifluoropropyl methyl siloxane.
 13. An injectable lensmaterial according to claim 1, wherein the polysiloxane has a viscosityof less than about 60,000 cSt.
 14. An injectable lens material havingsuitable viscosity for being injected through standard cannula andcomprising a mixture of a polysiloxane copolymer, a photoinitiator, and,optionally, a crosslinking agent, wherein the polysiloxane copolymer hasfunctional acryl groups at the terminal ends thereof capable of beingphotopolymerized into a solid intraocular lens, a specific gravitygreater than about 1.0, a refractive index suitable for restoring therefractive power of the natural crystalline lens, and siloxane monomerunits in the polysiloxane copolymer selected from the group consistingof substituted and unsubstituted arylsiloxanes, substituted andunsubstituted arylalkylsiloxanes, and substituted and unsubstitutedalkyl(alkyl)siloxanes, and wherein the photoinitiator is activated byblue light.